Surgical Treatment of Periimplantitis With Augmentative Techniques.

OBJECTIVES To address the focused question: "In patients with osseointegrated implants diagnosed with periimplantitis, what are the clinical and radiographic outcomes of augmentative surgical interventions compared with nonaugmentative surgical measures"? MATERIAL AND METHODS Literature screening was performed in MEDLINE through the PubMed database, for articles published until January 1, 2018. Human studies reporting on the clinical (ie, bleeding on probing [BOP] and probing depth [PD] changes) and/or radiographic (ie, periimplant defect reduction and/or fill) treatment outcomes after surgical augmentative periimplantitis therapy, and/or comparing augmentative and nonaugmentative surgical approaches were searched. RESULTS Thirteen comparative and 11 observational clinical studies were included. Surgical augmentative periimplantitis therapy resulted in mean BOP and PD reduction ranging from 26% to 91%, and 0.74 to 5.4 mm, respectively. The reported mean radiographic fill of intrabony defects ranged between 57% and 93.3%, and defect vertical reduction varied from 0.2 to 3.77 mm. Three randomized controlled clinical studies failed to demonstrate the superiority of augmentative therapy compared with nonaugmentative approach in terms of PD and BOP reduction. CONCLUSIONS The available evidence to support superiority of augmentative surgical techniques for periimplantitis management on the treatment outcomes over nonaugmentative methods is limited

No sex-specific difference in disease trajectory in multiple sclerosis patients before and after age 50

Background: The disease course in multiple sclerosis (MS) is influenced by many factors, including age, sex, and sex hormones. Little is known about sex-specific changes in disease course around age 50, which may represent a key biological transition period for reproductive aging. Methods: Male and female subjects with no prior chemotherapy exposure were selected from a prospective MS cohort to form groups representing the years before (38–46 years, N=351) and after (54–62 years, N=200)age 50. Primary analysis assessed for interaction between effects of sex and age on clinical (Expanded Disability Status Scale, EDSS; relapse rate) and radiologic (T2 lesion volume, T2LV; brain parenchymal fraction, BPF) outcomes. Secondarily, we explored patient-reported outcomes (PROs). Results: As expected, there were age- and sex- related changes with male and older cohorts showing worse disease severity (EDSS), brain atrophy (BPF), and more progressive course. There was no interaction between age and sex on cross-sectional adjusted clinical (EDSS, relapse rate) or radiologic (BPF, T2LV) measures, or on 2-year trajectories of decline. There was a significant interaction between age and sex for a physical functioning PRO (SF-36): the older female cohort reported lower physical functioning than men (p=0.002). There were no differences in depression (Center for Epidemiological Study – Depression, CES-D) or fatigue (Modified Fatigue Impact Scale, MFIS) scores. Conclusions: There was no interaction between age and sex suggestive of an effect of reproductive aging on clinical or radiologic progression. Prospective analyses across the menopausal transition are needed

Search for varying constants of nature from astronomical observation of molecules

The status of searches for possible variation in the constants of nature from astronomical observation of molecules is reviewed, focusing on the dimensionless constant representing the proton-electron mass ratio $\mu=m_p/m_e$. The optical detection of H$_2$ and CO molecules with large ground-based telescopes (as the ESO-VLT and the Keck telescopes), as well as the detection of H$_2$ with the Cosmic Origins Spectrograph aboard the Hubble Space Telescope is discussed in the context of varying constants, and in connection to different theoretical scenarios. Radio astronomy provides an alternative search strategy bearing the advantage that molecules as NH$_3$ (ammonia) and CH$_3$OH (methanol) can be used, which are much more sensitive to a varying $\mu$ than diatomic molecules. Current constraints are $|\Delta\mu/\mu| < 5 \times 10^{-6}$ for redshift $z=2.0-4.2$, corresponding to look-back times of 10-12.5 Gyrs, and $|\Delta\mu/\mu| < 1.5 \times 10^{-7}$ for $z=0.88$, corresponding to half the age of the Universe (both at 3$\sigma$ statistical significance). Existing bottlenecks and prospects for future improvement with novel instrumentation are discussed.Comment: Contribution to Workshop "High Performance Clocks in Space" at the International Space Science Institute, Bern 201

Maternal Occupational Exposure to Polycyclic Aromatic Hydrocarbons: Effects on Gastroschisis among Offspring in the National Birth Defects Prevention Study

Background: Exposure to polycyclic aromatic hydrocarbons (PAHs) occurs in many occupational settings. There is evidence in animal models that maternal exposure to PAHs during pregnancy is associated with gastroschisis in offspring; however, to our knowledge, no human studies examining this association have been conducted

A Phase 2 Study of Nivolumab Combined With Ibrutinib in Patients With Diffuse Large B-Cell Richter Transformation of CLL

Richter transformation (RT) is a rare complication of chronic lymphocytic leukemia (CLL) that has dismal outcomes. Upregulation of PD-1/PD-L1 drives immunological evasion in patients with RT. We hypothesized that combining nivolumab, a PD-1 blocking antibody, with the BTK inhibitor (BTKi) ibrutinib could potentiate tumor-cell killing. We conducted an investigator-initiated phase 2 clinical trial to assess the efficacy of combined nivolumab and ibrutinib in patients with diffuse large B-cell lymphoma (DLBCL) RT and CLL. Patients included were ≥18 years of age with adequate hepatic and renal function. Patients received nivolumab every 2 weeks of a 4-week cycle for a maximum of 24 cycles. A standard dose ibrutinib was initiated from cycle 2 onward and continued daily until progression. For patients who were already on ibrutinib at the time of study entry, the same was continued while nivolumab was initiated. A total of 24 patients with RT with a median age of 64.5 years (range, 47-88) were enrolled. Ten patients (42%) had received prior treatment for RT and 13 patients (54%) had received a prior BTKi. A total of 10 patients (42%) responded with a median duration of response of 15 months. The median overall survival was 13 months. Four of 24 (17%) patients had checkpoint inhibition-related immunological toxicities. In the CLL cohort, 10 patients were enrolled, of whom 3 patients converted from partial to complete remission; 1 patient had a grade 2 immunological toxicity. Combined nivolumab and ibrutinib is an active regimen for patients with DLBCL RT with an overall response rate of 42%. Given the limited treatment options for patients with RT, checkpoint inhibition provides a potential therapeutic option. This trial is registered at www.clinicaltrials.gov as #NCT02420912

Core Verbal Autopsy Procedures with Comparative Validation Results from Two Countries

BACKGROUND: Cause-specific mortality statistics remain scarce for the majority of low-income countries, where the highest disease burdens are experienced. Neither facility-based information systems nor vital registration provide adequate or representative data. The expansion of sample vital registration with verbal autopsy procedures represents the most promising interim solution for this problem. The development and validation of core verbal autopsy forms and suitable coding and tabulation procedures are an essential first step to extending the benefits of this method. METHODS AND FINDINGS: Core forms for peri- and neonatal, child, and adult deaths were developed and revised over 12 y through a project of the Tanzanian Ministry of Health and were applied to over 50,000 deaths. The contents of the core forms draw upon and are generally comparable with previously proposed verbal autopsy procedures. The core forms and coding procedures based on the International Statistical Classification of Diseases (ICD) were further adapted for use in China. These forms, the ICD tabulation list, the summary validation protocol, and the summary validation results from Tanzania and China are presented here. CONCLUSIONS: The procedures are capable of providing reasonable mortality estimates as adjudged against stated performance criteria for several common causes of death in two countries with radically different cause structures of mortality. However, the specific causes for which the procedures perform well varied between the two settings because of differences in the underlying prevalence of the main causes of death. These differences serve to emphasize the need to undertake validation studies of verbal autopsy procedures when they are applied in new epidemiological settings

Observing the Evolution of the Universe

How did the universe evolve? The fine angular scale (l>1000) temperature and polarization anisotropies in the CMB are a Rosetta stone for understanding the evolution of the universe. Through detailed measurements one may address everything from the physics of the birth of the universe to the history of star formation and the process by which galaxies formed. One may in addition track the evolution of the dark energy and discover the net neutrino mass. We are at the dawn of a new era in which hundreds of square degrees of sky can be mapped with arcminute resolution and sensitivities measured in microKelvin. Acquiring these data requires the use of special purpose telescopes such as the Atacama Cosmology Telescope (ACT), located in Chile, and the South Pole Telescope (SPT). These new telescopes are outfitted with a new generation of custom mm-wave kilo-pixel arrays. Additional instruments are in the planning stages.Comment: Science White Paper submitted to the US Astro2010 Decadal Survey. Full list of 177 author available at http://cmbpol.uchicago.ed